E.M. Gilbert

Magnitude and time course of changes induced by continuous-flow left ventricular assist device unloading in chronic heart failure: insights into cardiac recovery.

OBJECTIVES This study sought to prospectively investigate the longitudinal effects of continuous-flow left ventricular assist device (LVAD) unloading on myocardial structure and systolic and diastolic function. BACKGROUND The magnitude, timeline, and sustainability of changes induced by continuous-flow LVAD on the structure and function of the failing human heart are unknown. METHODS Eighty consecutive patients with clinical characteristics consistent with chronic heart failure requiring implantation of a continuous-flow LVAD were prospectively enrolled. Serial echocardiograms (at 1, 2, 3, 4, 6, 9, and 12 months) and right heart catheterizations were performed after LVAD implant. Cardiac recovery was assessed on the basis of improvement in systolic and diastolic function indices on echocardiography that were sustained during LVAD turn-down studies. RESULTS After 6 months of LVAD unloading, 34% of patients had a relative LV ejection fraction increase above 50% and 19% of patients, both ischemic and nonischemic, achieved an LV ejection fraction ≥ 40%. LV systolic function improved as early as 30 days, the greatest degree of improvement was achieved by 6 months of mechanical unloading and persisted over the 1-year follow up. LV diastolic function parameters also improved as early as 30 days after LVAD unloading, and this improvement persisted over time. LV end-diastolic and end-systolic volumes decreased as early as 30 days after LVAD unloading (113 vs. 77 ml/m(2), p < 0.01, and 92 vs. 60 ml/m(2), p < 0.01, respectively). LV mass decreased as early as 30 days after LVAD unloading (114 vs. 95 g/m(2), p < 0.05) and continued to do so over the 1-year follow-up but did not reach values below the normal reference range, suggesting no atrophic remodeling after prolonged LVAD unloading. CONCLUSIONS Continuous-flow LVAD unloading induced in a subset of patients, both ischemic and nonischemic, early improvement in myocardial structure and systolic and diastolic function that was largely completed within 6 months, with no evidence of subsequent regression.

Utility of virtual crossmatch in sensitized patients awaiting heart transplantation.

BACKGROUND Organ transplant candidates with serum antibodies directed against human leukocyte antigens (HLA) face longer waiting times and higher mortality while awaiting transplantation. This study examined the accuracy of virtual crossmatch, in which recipient HLA-specific antibodies, identified by solid-phase assays, are compared to the prospective donor HLA-type in heart transplantation. METHODS We examined the accuracy of virtual crossmatch in predicting immune compatibility of donors and recipients in heart transplantation and clinical outcomes in immunologically sensitized heart transplant recipients in whom virtual crossmatch was used in allograft allocation. RESULTS Based on analysis of 257 T-cell antihuman immunoglobulin complement-dependent cytotoxic (AHG-CDC) crossmatch tests, the positive predictive value of virtual crossmatch (the likelihood of an incompatible virtual crossmatch resulting in an incompatible T-cell CDC-AHG crossmatch) was 79%, and the negative predictive value of virtual crossmatch (the likelihood of a compatible virtual crossmatch resulting in a compatible T-cell CDC-AHG crossmatch) was 92%. When used in a cohort of 28 sensitized patients awaiting heart transplantation, 14 received allografts based on a compatible virtual crossmatch alone from donors in geographically distant locations. Compared with the other 14 sensitized patients who underwent transplant after a compatible prospective serologic crossmatch, the rejection rates and survival were similar. CONCLUSION Our findings are evidence of the accuracy of virtual crossmatch and its utility in augmenting the opportunities for transplantation of sensitized patients.

Tuberculosis in a Solid-organ Transplant Recipient: Modern-day Implications

The clinical presentation and disease course of tuberculosis (TB) in a solid-organ transplant (SOT) recipient may be atypical and the risk of mortality is high. Herein we examine the role of the different tests used in diagnosis of TB and review the specifics of anti-mycobacterial therapy and the public health implications of TB in a SOT recipient.

Left ventricular perforation after Impella® placement in a patient with cardiogenic shock

Mechanical cardiovascular support devices are now widely used both in the setting of cardiogenic shock as well as during high risk cardiac catheterization procedures. We report a case of a young female patient who presented with presumed myocarditis and rapidly deteriorating decompensated heart failure requiring the implantation of an Impella Circulatory Support System. Upon transfer to our facility it was discovered that during transport, the Impella device had migrated through the left ventricle. She was emergently taken to the operating room where the Impella was surgically removed and biventricular support devices were placed. The patient eventually expired after weeks of treatment in the intensive care unit. We believe this is the first recorded case of an Impella device perforating the left ventricle. Particularly in cases of newly discovered pericardial effusion, change in waveform on the Impella controller placement signal or rapid decompensation, physicians should consider this rare but potentially catastrophic complication associated with mechanical left ventricular support devices.

Recovery of Myocardial Capillary Bed (Microvascular) Density Persists in Long Term Follow Up of CAV Patients Treated With Sirolimus

(r= 0.45, p< 0.001), age (r= 0.33, p< 0.01), time after transplantation (r= 0.23, p< 0.05), copeptin (r= -0.42, p< 0.001), sTfR (r= 0.24, p< 0.05), hemoglobin (r= -0.42, p< 0.001), transferrin (r= -0.31, p< 0.01) haptoglobin (r= 0.39, p< 0.001), cystatin C (r= 0.55, p< 0.001), ejection fraction-EF (r= -0.28, p< 0.05), NYHA class (r= -0.41, p< 0.01) hsCRP (r= 0.26, p< 0.05), IL-6 (r= 0.23, p< 0.05), vWF (r= -0.40, p< 0.001) and midkine (r= 0.33, p< 0.01). In multivariate analysis, only creatinine was found to be predictor of YKL-40 (beta value 0.59, p= 0.02), explaining 56% of the variation in YKL-40 levels in heart allograft recipients. Conclusion: YKL-40 may contribute to the enhanced risk of cardiovascular complications mainly due to impaired renal function in patients after heart transplantation.

Fibrin on Endomyocardial Biopsy: A Significant Predictor of Cardiovascular Mortality beyond pAMR Score

Purpose Endothelial activation (EA) is the hallmark lesion of antibody-mediated rejection (AMR). Mediators of EA trigger a cascade of additional endothelial injury leading to plasma protein leakage and fibrin accumulation. We hypothesized that interstitial fibrin on endomyocardial biopsy (EMB) would correlate with AMR severity and worse outcomes. Methods and Materials The AMR scores of patients transplanted in the UTAH Cardiac Transplant Program between 1986 and 2012 were classified according to the new ISHLT nomenclature. A semiquantitative scale (0-5) was used to record the presence of fibrin in the interstitium (FInt) and vessels (FVasc) (0, no fibrin; 5, diffuse fibrin). Cox proportional hazard models were fit with cardiovascular (CV) death or retransplant as the outcome. The pAMR value was included as a categorical variable and the fibrin variables were included in separate models as additive continuous variables. Both pAMR and fibrin were measured from last biopsy and varied over the time of the study. Results 11,550 biopsies from 983 patients were analyzed. Across all pAMR values, the presence of any fibrin increased the risk of CV mortality (OR 2.8, p=0.002). On further analysis, for each one unit increase in the FInt score, an additional 20% increase in CV mortality, above that due to pAMR alone, was observed (p=0.005). In contrast, the severity of the Fvasc score did not further increase the risk of CV death beyond that due to pAMR score (p=0.359). Conclusions The presence of interstitial fibrin on EMB confers an incremental risk of CV mortality in heart transplant recipients above that due to pAMR severity alone. This may be related to a more severe and chronic form of AMR in certain patients. Whether fibrin should be required as part of the pAMR grading system warrants serious consideration. Odds ratio for CV mortality stratified by pAMR score and fibrin deposition Interstitial Fibrin 0 1 2 3 4 5 pAMR0 1.00 1.20 1.45 1.74 2.09 2.52 pAMR1 2.37 2.85 3.43 4.12 4.96 5.97 pAMR2 3.21 3.86 4.64 5.58 6.71 8.08 pAMR3 61.51 73.99 88.99 107.03 128.73 154.83

508 Microvessel Density in Cardiac Allograft Biopsies in Patients with Clinically Significant Coronary Allograft Vasculopathy Treated with Sirolimus

ROC Area 0.64 vs 0.75 0.71 vs 0.78 0.93 vs 0.96 0.75 vs 0.78 0.88 vs 0.92 0.86 vs 0.87 Sensitivity 0.56 vs 0.94 0.66 vs 0.62 0.90 vs 1.00 0.65 vs 0.79 0.71 vs 1.00 0.87 vs 0.87 Specificity 0.71 vs 0.54 0.68 vs 0.86 0.82 vs 0.86 0.75 vs 0.68 0.90 vs 0.72 0.74 vs 0.75 PPV 0.31 vs 0.32 0.78 vs 0.88 0.24 vs 0.30 0.56 vs 0.55 0.23 vs 0.13 0.43 vs 0.43 NPV 0.88 vs 0.97 0.54 vs 0.57 0.99 vs 1.00 0.81 vs 0.87 0.99 vs 1.00 0.96 vs 0.96 Prevalence 0.19 0.63 0.06 0.33 0.04 0.18 Cutoff Value 0.13 vs 0.12 0.45 vs 0.70 0.02 vs 0.05 0.35 vs 0.29 0.03 vs 0.02 0.12 vs 0.11 ROC: Receiver Operating Characteristic; PPV: Positive Predictive Value; NPV: Negative Predictive Value

359: Virtual crossmatch improves organ allocation in sensitized patients

Purpose: Heart transplantation (tx) in patients with human leukocyte antigen (HLA) sensitization presents challenges in organ allocation. A requirement of a conventional prospective crossmatch effectively halts the use of distant donors (DD) in these patients, resulting in longer wait times. The use of ‘virtual crossmatch’, in which the sensitized recipients’ HLA antibody profiles are determined by Class I and II LabScreen® PRA beads on a Luminex platform and compared to the antigen profile of the donor, could increase the use of allografts from DD. Methods and Materials: All sensitized recipients tx since 2001 in whom antibodies to specific Class I and II HLA antigens were identified were included in the analysis. For these patients, conventional prospective crossmatch was required when allografts were procured from local donors (LD), while virtual crossmatch was required when allografts were procured from DD. Results: Thirty-one patients met the inclusion criteria. Fifteen patients received allografts from LD with negative conventional prospective crossmatch. Sixteen patients (52%) were transplanted with allografts from DD with negative virtual crossmatch. Detailed clinical outcomes data are listed in Table 1. Of note, three of the DD patients had a positive retrospective crossmatch, were treated with plasmapheresis and all three are alive. Conclusions: Virtual crossmatch by HLA typing allowed utilization of allografts from DD in more than half of sensitized patients. While antibody-mediated rejection was more common with tx from DD, intermediate-term mortality was not unfavorably affected. Virtual crossmatch in heart tx is likely to improve organ allocation in sensitized patients.